The aim of this project is the study of normal and abnormal cell differentiation, particularly the reversible suppression of malignancy and pigmentation in melanoma cell culture by 5-bromodeoxyuridine (BrdU). These cells normally form tumors in all C57BL/6J adult mice injected. They lose malignancy and pigment after growth in 1-3 micrograms/ml of BrdU for as little as 24 hours. If maintained in BrdU these cells grow in a "contact-inhibited" fibroblastic fashion and remain non- tumorigenic. They can immunize mice against their malignant parental line. Although unable to form tumors in normal adult mice, they can do so in neonates and antilymphocyte-treated adults. Unlike untreated cells, they produce a C-type virus which fuses many cell types, forming polykaryocytes. The virus is capable of cell hybridization with some lines. It has not caused a melanoma in more than 100 neonates inoculated, but did protect 45/114 babies that were challenged with melanoma 30 days after birth. Adults were not protected by the same treatment. Tyrosinase synthesis is completely suppressed by 6 days after treatment and 80 percent reduced by 3 days, at which time DNA, RNA and protein synthesis remained at normal levels. Thus BrdU seems to be selective in suppression of synthesis of specific macromolecules.